Deciphering the mechanisms mediating the dichotomous effects of fever on brain function and behavior

动物护理和使用委员会于2023年7月29日批准了“解密介导发热对脑功能和行为的二分效应的机制”的动物方案更新。尽管2019冠状病毒病疫情带来挑战，影响了2020年及2021年的研究进展，但我们在各个研究领域取得了重大进展。具体而言，我们有： 1.确定了导致ASD（自闭症谱系障碍）个体某些类型学习缺陷的大脑网络和机制。 2.证明暴露于发热温度单独可以有效地缓解ASD症状，由于独特的影响，抑制特定电压门控通道的活动。 3.表明发烧可以调节大脑皮层的整体活动水平。 4.揭示了在发育中的皮层中特异性激活的神经回路机制，以在发烧期间保护大脑。 目前，我们正在修订或编写报告这些重要调查结果的文稿。我们未来的努力将涉及扩展我们研究结果的适用性，以涵盖与ASD易感性增加相关的四种主要遗传变异。此外，我们将在最近建立的环境诱导ASD模型中验证我们的发现。这些目标的成功实现将大大推进我们的努力，使有针对性地使用诱导发热样温度的药物作为ASD症状的治疗方法。

The renewal of the animal protocol for "Deciphering the mechanisms mediating the dichotomous effects of fever on brain function and behavior" was approved by the Animal Care and Use Committee on 07/29/2023. Despite the challenges posed by the COVID-19 pandemic, which impacted research progress in 2020 and 2021, we have made significant strides in various study areas. Specifically, we have: 1. Identified brain networks and mechanisms that contribute to certain types of learning deficits in individuals with ASD (Autism Spectrum Disorder). 2. Demonstrated that exposure to febrile temperatures alone can effectively alleviate ASD symptoms, owing to unique effects that dampen activity in specific voltage-gated channels. 3. Shown that fever can modulate overall activity levels in the cortex. 4. Uncovered neural circuit mechanisms that are specifically activated in the developing cortex to safeguard the brain during fever. At present, we are in the process of revising or preparing manuscripts to report these significant findings. Our future endeavors will involve extending the applicability of our findings to encompass four primary genetic variants associated with heightened susceptibility to ASD. Additionally, we will validate our discoveries within a recently established environmental-induced ASD model. The successful achievement of these objectives will significantly advance our efforts to enable the targeted use of pharmacological agents that induce fever-like temperatures as a treatment approach for ASD symptoms.